Modern scientific investigations frequently involve the use of large number of chemical reactions. For efficient implementation, these reactions are preferably run using systems that minimize setup times and cost while ensuring the quality of their results.
In many cases, a multiplicity of reactions are performed on systems in which a small set of reactants are combined with a much larger set of reactants. For example, a single biological sample may be subjected to a multiplicity of polymerase chain reactions, each of which address the expression level of a single gene.
Many different chemical, biochemical, and other reactions are also sensitive to small temperature variations. The reactions may be enhanced or inhibited based on the temperatures of the materials involved. In many such reactions, a temperature variation of even 1 or 2 degrees Celsius may have a significantly adverse impact on the reaction. Although it may be possible to process samples individually and obtain accurate sample-to-sample results, individual processing can be time-consuming and expensive.
One approach to reducing the time and cost of processing multiple samples is to use a device including multiple chambers in which different portions of one sample or different samples can be processed simultaneously. However, this approach presents several temperature control related issues. When using multiple chambers, the temperature uniformity from chamber to chamber may be difficult to control. Another problem involves the speed or rate at which temperature transitions occur when thermal processing, such as when thermal cycling. Still another problem is the overall length of time required to thermal cycle a sample(s).
The multiple chamber device may include a distribution system. However, the distribution system presents the potential for cross-contamination. Sample may inadvertently flow among the chambers during processing, thereby potentially adversely impacting the reaction(s) occurring in the chambers. This may be particularly significant when multiple samples are being processed. In addition, the distribution system may present problems when smaller than usual samples are available, because the distribution system is in fluid communication with all of the process chambers. As a result, it is typically not possible to prevent delivery of sample materials to all of the process chambers to adapt to the smaller volume samples.
Thermal processing, in and of itself, presents an issue in that the materials used in the devices may need to be robust enough to withstand repeated temperature cycles during, e.g., thermal cycling processes such as PCR. The robustness of the devices may be more important when the device uses a sealed or closed system. Also, it is often required that the process chambers remain in adequate alignment with instrument optics despite temperature changes and the attendant thermal expansion.
Various sample processing devices of the present invention are described in U.S. Provisional Patent Application Ser. No. 60/214,508 filed on 28 Jun. 2000 and titled THERMAL PROCESSING DEVICES AND METHODS; U.S. Provisional Patent Application Ser. No. 60/214,642 filed on 28 Jun. 2000 and titled SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS; U.S. Provisional Patent Application Ser. No. 60/237,072 filed on 2 Oct. 2000 and titled SAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS; U.S. patent application Ser. No. 09/710,184, filed 10 Nov. 2000, titled CENTRIFUGAL FILLING OF SAMPLE PROCESSING DEVICES, U.S. patent application Ser. No. 09/895,001, filed 28 Jun. 2001, and titled SAMPLE PROCESSING DEVICES AND CARRIERS; U.S. patent application Ser. No. 09/895,010, filed 28 Jun. 2001, and titled SAMPLE PROCESSING DEVICES.
The documents identified above all disclose a variety of different constructions of sample processing devices that could be used to manufacture sample processing devices according to the principles of the present invention. For example, although many of the sample processing devices described herein are attached using adhesives (e.g., pressure sensitive adhesives), devices of the present invention could be manufactured using heat sealing or other bonding techniques.
Although the devices and their carriers identified in the above-listed patent documents may provide many advantages over the prior art, further improvements may still be possible. For example, the use of a carrier separate from the sample processing device may add cost to the sample processing devices as delivered to customers because of the need to manufacture different components separately from each other and then accurately assemble the components. In addition to adding cost, inaccurate assembly may cause performance problems due to misalignment of interrogation zones with the optics train of the analytical device. Further variability in the assembly process may induce unwanted part-to-part variability in the way the assembly fits to the thermal platen and hence thermal variations between process chambers.